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Inhibitory activity of coumarins from Artemisia capillaris against advanced glycation endproduct formation

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Abstract

Since glycation can lead to the onset of diabetic complications due to chronic hyperglycemia, several indigenous Artemisia species were evaluated as potential inhibitors of advanced glycation endproducts (AGE). Among them, the Artemisia capillaris plant demonstrated the highest AGE inhibitory activity. Repeated column chromatography was performed to isolate a new acylated flavonoid glycoside, acacetin-7-O-(6″-O-acetyl)-β-d-glucopyranosyl-(1→2)[α-l-rhamnopyranosyl]-(1→6)-β-d-glucopyranoside, along with 11 known flavonoids (acacetin-7-O-β-d-glucopyranosyl-(1→2)[α-l-rhamnopyranosyl]-(1→6)-β-d-glucopyranoside, linarin, quercetin, hyperoside, isorhamnetin, isorhamnetin 3-galactoside, isorhamnetin 3-glucoside, isorhamnetin 3-arabinoside, isorhamnetin 3-robinobioside, arcapillin, and cirsilineol), six coumarins (umbelliferone, esculetin, scopoletin, scopolin, isoscopolin, and scoparone), and two phenolic derivatives (4,5-di-O-caffeoylquinic acid and chlorogenic acid). In determining the structure-activity relationship (SAR), it was found that the presence and position of hydroxyl group of test coumarins (coumarin, esculin, isoscopoletin, daphnetin, 4-methylcoumarin, and six isolated coumarins) may play a crucial role in AGE inhibition. A free hydroxyl group at C-7 and a glucosyl group instead of a methoxyl group at C-6 are two important parameters for the inhibitory potential of coumarins on AGE formation. A. capillaris and five key AGE inhibitors, including 4,5-di-Ocaffeoylquinic acid, umbelliferone, esculetin, esculin, and scopoletin, were identified as potential candidates for use as therapeutic or preventive agents for diabetic complications and oxidative stress-related diseases. We understand this to be the first detailed study on the SAR of coumarins in AGE inhibition.

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References

  • Ahmed, N., Advanced glycation endproducts-role in pathology of diabetic complications. Diabetes Res. Clin. Pract., 67, 3–21 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Ahmed, N. and Thornalley, P. J., Advanced glycation endproducts: what is their relevance to diabetic complications? Diabetes Obes. Metab., 9, 233–245 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Altan, V. M., The pharmacology of diabetic complications. Curr. Med. Chem., 10, 1317–1327 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Bayoumi, S. A., Rowan, M. G., Beeching, J. R., and Blagbrough, I. S., Constituents and secondary metabolite natural products in fresh and deteriorated cassava roots. Phytochemistry, 71, 598–604 (2010).

    Article  PubMed  CAS  Google Scholar 

  • Blois, M. S., Antioxidant determination by the use of a stable free radical. Nature, 181, 1199–1200 (1958).

    Article  CAS  Google Scholar 

  • Cha, J. D., Moon, S. E., Kim, H. Y., Cha, I. H., and Lee, K. Y., Essential oil of Artemisia capillaris induces apoptosis in KB cells via mitochondrial stress and caspase activation mediated by MAPK-stimulated signaling pathway. J. Food Sci., 74, T75–81 (2009).

    Article  PubMed  CAS  Google Scholar 

  • Chen, Y. L., Huang, H. C., Weng, Y. I., Yu, Y. J., and Lee, Y. T., Morphological evidence for the antiatherogenic effect of scoparone in hyperlipidaemic diabetic rabbits. Cardiovasc. Res., 28, 1679–1685 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Choi, J. H., Kim, D. W., Yun, N., Choi, J. S., Islam, M. N., Kim, Y. S., and Lee, S. M., Protective effects of hyperoside against carbon tetrachloride-induced liver damage in mice. J. Nat. Prod., 74, 1055–1060 (2011).

    Article  PubMed  CAS  Google Scholar 

  • Cui, C.-B., Jeong, S. K., Lee, Y. S., Lee, S. O., Kang, I.-J., and Lim, S. S., Inhibitory activity of caffeoylquinic acids from the aerial parts of Artemisia princeps on rat lens aldose reductase and on the formation of advanced glycation end products. J. Korean Soc. Appl. Biol. Chem., 52, 655–662 (2009).

    Article  CAS  Google Scholar 

  • de la Fuente, J. A. and Manzanaro, S., Aldose reductase inhibitors from natural sources. Nat. Prod. Rep., 20, 243–251 (2003).

    Article  PubMed  Google Scholar 

  • Hayman, S. and Kinoshita, J. H., Isolation and properties of lens aldose reductase. J. Biol. Chem., 240, 877–882 (1965).

    PubMed  CAS  Google Scholar 

  • Hong, J. H., Hwang, E. Y., Kim, H. J., Jeong, Y. J., and Lee, I. S., Artemisia capillaris inhibits lipid accumulation in 3T3-L1 adipocytes and obesity in C57BL/6J mice fed a high fat diet. J. Med. Food, 12, 736–745 (2009).

    Article  PubMed  Google Scholar 

  • Hong, J. H. and Lee, I. S., Cytoprotective effect of Artemisia capillaris fractions on oxidative stress-induced apoptosis in V79 cells. Biofactors, 35, 380–388 (2009a).

    Article  PubMed  CAS  Google Scholar 

  • Hong, J. H. and Lee, I. S., Effects of Artemisia capillaris ethyl acetate fraction on oxidative stress and antioxidant enzyme in high-fat diet induced obese mice. Chem. Biol. Interact., 179, 88–93 (2009b).

    Article  PubMed  CAS  Google Scholar 

  • Hong, J. H., Lee, J. W., Park, J. H., and Lee, I. S., Antioxidative and cytoprotective effects of Artemisia capillaris fractions. Biofactors, 31, 43–53 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Hong, S. H., Seo, S. H., Lee, J. H., and Choi, B. T., The aqueous extract from Artemisia capillaris Thunb. inhibits lipopolysaccharide-induced inflammatory response through preventing NF-κB activation in human hepatoma cell line and rat liver. Int. J. Mol. Med., 13, 717–720 (2004).

    PubMed  Google Scholar 

  • Jang, S. I., Kim, Y. J., Lee, W. Y., Kwak, K. C., Baek, S. H., Kwak, G. B., Yun, Y. G., Kwon, T. O., Chung, H. T., and Chai, K. Y., Scoparone from Artemisia capillaris inhibits the release of inflammatory mediators in RAW 264.7 cells upon stimulation cells by interferon-γ Plus LPS. Arch. Pharm. Res., 28, 203–208 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Jeong, S. H., Han, X. H., Hong, S. S., Hwang, J. S., Hwang, J. H., Lee, D., Lee, M. K., Ro, J. S., and Hwang, B. Y., Monoamine oxidase inhibitory coumarins from the aerial parts of Dictamnus albus. Arch. Pharm. Res., 29, 1119–1124 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Jung, H. A., Islam, M. D., Kwon, Y. S., Jin, S. E., Son, Y. K., Park, J. J., Sohn, H. S., and Choi, J. S., Extraction and identification of three major aldose reductase inhibitors from Artemisia montana. Food Chem. Toxicol., 49, 376–384 (2011).

    Article  PubMed  CAS  Google Scholar 

  • Jung, U. J., Baek, N. I., Chung, H. G., Bang, M. H., Yoo, J. S., Jeong, T. S., Lee, K. T., Kang, Y. J., Lee, M. K., Kim, H. J., Yeo, J. Y., and Choi, M. S., The anti-diabetic effects of ethanol extract from two variants of Artemisia princeps Pampanini in C57BL/KsJ-db/db mice. Food Chem. Toxicol., 45, 2022–2029 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Jung, H. A. Lee, B. J. Moon, S. G., Lee, H. J., Kim, Y. A., Park, K. E., Ahn, J. W., and Seo, Y. W., Antioxidant activity of Artemisia capillaris Thunberg. Food Sci. Biotechnol., 13, 328–331 (2004).

    CAS  Google Scholar 

  • Kariyone, T., Takahashi, M., Ito, T., and Masutani, K., Chemical constituents of the plants of Coniferae and allied orders XXXIII A new glycoside, distichin, and other constituents of the leaves of Taxodium distichum. Yakugaku Zasshi, 80, 102–105 (1960).

    CAS  Google Scholar 

  • Kato, A., Kobayashi, K., Narukawa, K., Minoshima, Y., Adachi, I., Hirono, S., and Nash, R. J., 6,7-Dihydroxy-4-phenylcoumarin as inhibitor of aldose reductase 2. Bioorg. Med. Chem. Lett., 20, 5630–5633 (2010).

    Article  PubMed  CAS  Google Scholar 

  • Kato, A., Minoshima, Y., Yamamoto, J., Adachi, I., Watson, A. A., and Nash, R. J., Protective effects of dietary chamomile tea on diabetic complications. J. Agric. Food Chem., 56, 8206–8211 (2008).

    Article  PubMed  CAS  Google Scholar 

  • Kheterpal, I., Coleman, L., Ku, G., Wang, Z. Q., Ribnicky, D., and Cefalu, W. T., Regulation of insulin action by an extract of Artemisia dracunculus L. in primary human skeletal muscle culture: a proteomics approach. Phytother. Res., 24, 1278–1284 (2010).

    Article  PubMed  CAS  Google Scholar 

  • Kiso, Y., Ogasawara, S., Hirota, K., Watanabe, N., Oshima, Y., Konno, C., and Hikino, H., Antihepatotoxic principles of Artemisia capillaris Buds 1. Planta Med., 50, 81–85 (1984).

    Article  CAS  Google Scholar 

  • Kochakian, M., Chronic dosing with aminoguanidine and novel advanced glycosylation end product-formation inhibitors ameliorates cross-linking of tail tendon collagen in STZ-induced diabetic rats. Diabetes, 45, 1694–1700 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Kooy, N. W., Royall, J. A., Ischiropoulos, H., and Beckman, J. S., Peroxynitrite-mediated oxidation of dihydrorhodamine 123. Free Radic. Biol. Med., 16, 149–156 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Kordali, S., Cakir, A., Mavi, A., Kilic, H., and Yildirim, A., Screening of chemical composition and antifungal and antioxidant activities of the essential oils from three Turkish Artemisia species. J. Agric. Food Chem., 53, 1408–1416 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Kwon, O. S., Choi, J. S., Islam, M. N., Kim, Y. S., and Kim, H. P., Inhibition of 5-lipoxygenase and skin inflammation by the aerial parts of Artemisia capillaris and its constituents. Arch. Pharm. Res., 34, 1561–1569 (2011).

    Article  PubMed  CAS  Google Scholar 

  • Lee, B. C., Lee, S. Y., Lee, H. J., Sim, G. S., Kim, J. H., Kim, J. H., Cho, Y. H., Lee, D. H., Pyo, H. B., Choe, T. B., Moon, D. C., Yun, Y. P., and Hong, J. T., Anti-oxidative and photoprotective effects of coumarins isolated from Fraxinus chinensis. Arch. Pharm. Res., 30, 1293–1301 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Lee, Y. S., Lee, S., Lee, H. S., Kim, B. K., Ohuchi, K., and Shin, K. H., Inhibitory effects of isorhamnetin-3-O-β-D-glucoside from Salicornia herbacea on rat lens aldose reductase and sorbitol accumulation in streptozotocin-induced diabetic rat tissues. Biol. Pharm. Bull., 28, 916–918 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Lee, C. J., Kim, H. H., Kim, J. D., and Kim, C. H., Effects of Artemisiae capillaris Fructus on experimental liver damage by carbon tetrachloride. Kor. J. Orient. Int. Med., 21, 100–107 (2000).

    Google Scholar 

  • Lee, H.-I., Seo, K.-O., Yun, K. W., Kim, M.-J., and Lee, M.-K. Comparative study of the hepatoprotective efficacy of Artemisia iwayomogi and Artemisia capillaris on ethanoladministered mice. J. Food Sci., 76, T207–T211 (2011).

    Article  PubMed  CAS  Google Scholar 

  • Lee, S., Jung, S. H., Lee, Y. S., Yamada, M., Kim, B. K., Ohuchi, K., and Shin, K. H., Antiinflammatory activity of hyperin from Acanthopanax chiisanensis roots. Arch. Pharm. Res., 27, 628–632 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Li, H., Zhang, Y., Wang, H., Zheng, X., and Chen, X., Nicousamide blocks the effects of advanced glycation end products on renal cells. Eur. J. Pharmacol., 674, 455–459 (2012).

    Article  PubMed  CAS  Google Scholar 

  • Li, H., Zheng, X., Wang, H., Zhang, Y., Xin, H., and Chen, X., XLF-III-43, a novel coumarin?aspirin compound, prevents diabetic nephropathy in rats via inhibiting advanced glycation end products. Eur. J. Pharmacol., 627, 340–347 (2010).

    Article  PubMed  CAS  Google Scholar 

  • Liu, Z. L., Chu, S. S., and Liu, Q. R., Chemical composition and insecticidal activity against Sitophilus zeamais of the essential oils of Artemisia capillaris and Artemisia mongolica. Molecules, 15, 2600–2608 (2010).

    Article  PubMed  CAS  Google Scholar 

  • Logendra, S., Ribnicky, D. M., Yang, H., Poulev, A., Ma, J., Kennelly, E. J., and Raskin, I., Bioassay-guided isolation of aldose reductase inhibitors from Artemisia dracunculus. Phytochemistry, 67, 1539–1546 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Markham, K. R., Ternai, B., Stanley, R., Geiger, H., and Mabry, T. J., Carbon-13 NMR studies of flavonoids-III: naturally occurring flavonoid glycosides and their acylated derivatives. Tetrahedron, 34, 1389–1397 (1978).

    Article  CAS  Google Scholar 

  • Matsuda, H., Wang, T., Managi, H., and Yoshikawa, M., Structural requirements of flavonoids for inhibition of protein glycation and radical scavenging activities. Bioorg. Med. Chem., 11, 5317–5323 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Muthenna, P., Akileshwari, C., Saraswat, M., and Bhanuprakash Reddy, G., Inhibition of advanced glycation end-product formation on eye lens protein by rutin. Brit. J. Nutr., 25, 1–9 (2011).

    Google Scholar 

  • Nakatani, N., Kayano, S., Kikuzaki, H., Sumono, K., Katagiri, K., and Mitani, T., Identification, quantitative determination, and antioxidative activities of chlorogenic acid isomers in Prune (Prunus domestica L.). J. Agric. Food Chem., 48, 5512–5516 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Nazaruk, J. and Gudej, J., Flavonoid compounds from the flowers of Cirsium rivulare (Jacq.) All. Acta Pol. Pharm., 60, 87–89 (2003).

    PubMed  CAS  Google Scholar 

  • Nicolle, E., Souard, F., Faure, P., and Boumendjel, A., Flavonoids as promising lead compounds in type 2 diabetes mellitus: molecules of interest and structure-activity relationship. Curr. Med. Chem., 18, 2661–2672 (2011).

    Article  PubMed  CAS  Google Scholar 

  • Numata, A., Hokimoto, K., and Yamaguchi, H., C-glycosylflavones in Lespedeza cuneata. Chem. Pharm. Bull., 28, 964–965 (1980).

    Article  CAS  Google Scholar 

  • Okuno, I., Uchida, K., Kadowaki, M., and Akahori, A., Choleretic effect of Artemisia capillaris extract in rats. Jpn. J. Pharmacol., 31, 835–838 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Pari, L. and Rajarajeswari, N., Efficacy of coumarin on hepatic key enzymes of glucose metabolism in chemical induced type 2 diabetic rats. Chem. Biol. Interact., 181, 292–296 (2009).

    Article  PubMed  CAS  Google Scholar 

  • Pari, L. and Rajarajeswari, N., Protective role of coumarin on plasma and tissue glycoprotein components in streptozotocin-nicotinamide induced hyperglycemic rats. Int. J. Biol. Med. Res., 1, 61–65 (2010).

    Google Scholar 

  • Park, H. Y., Kwon, S. B., Heo, N. K., Chun, W. J., Kim, M. J., and Kwon, Y. S., Constituents of the stem of Angelica gigas with rat lens aldose reductase inhibitory activity. J. Korean Soc. Appl. Biol. Chem., 54, 194–199 (2011).

    CAS  Google Scholar 

  • Park, K. H., Park, M., Choi, S. E., Jeong, M. S., Kwon, J. H., Oh, M. H., Choi, H. K., Seo, S. J., and Lee, M. W., The antioxidative and anti-inflammatory effects of caffeoyl derivatives from the roots of Aconitum koreanum R. RAYMOND. Biol. Pharm. Bull., 32, 2029–2033 (2009).

    Article  PubMed  CAS  Google Scholar 

  • Peyrou, J. and Sternberg, M., Advanced glycation endproducts (AGEs): Pharmacological inhibition in diabetes. Pathol. Biol., 54, 405–419 (2006).

    Article  Google Scholar 

  • Rahbar, S. and Figarola, J. L., Novel inhibitors of advanced glycation endproducts. Arch. Biochem. Biophys., 419, 63–79 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Rahbar, S., Novel inhibitors of glycation and AGE formation. Cell Biochem. Biophys., 48, 147–157 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Rajarajeswari, N. and Pari, L., Antioxidant role of coumarin on streptozotocin-nicotinamide-induced type 2 diabetic rats. J. Biochem. Mol. Toxicol., 25, 355–361 (2011).

    Article  PubMed  CAS  Google Scholar 

  • Ramesh, B. and Pugalendi, K. V., Effect of umbelliferone on tail tendon collagen and haemostatic function in streptozotocindiabetic rats. Basic Clin. Pharmacol. Toxicol., 101, 73–77 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Re, R., Pellegrini, N., Proteggente, A., Pannala, A., Yang, M., and Rice-Evans, C., Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic. Biol. Med., 26, 1231–1237 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Ribnicky, D. M., Kuhn, P., Poulev, A., Logendra, S., Zuberi, A., Cefalu, W. T., and Raskin, I., Improved absorption and bioactivity of active compounds from an anti-diabetic extract of Artemisia dracunculus L. Int. J. Pharm., 370, 87–92 (2009).

    Article  PubMed  CAS  Google Scholar 

  • Sasaki, N., Fukatsu, R., Tsuzuki, K., Hayashi, Y., Yoshida, T., Fujii, N., Koike, T., Wakayama, I., Yanagihara, R., Garruto, R., Amano, N., and Makita, Z., Advanced glycation end products in Alzheimer’s disease and other neurodegenerative diseases. Am. J. Pathol., 153, 1149–1155 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Seo, K. S., Jeong, H. J., and Yun, K. W., Antimicrobial activity and chemical components of two plants, Artemisia capillaris and Artemisia iwayomogi, used as Korean herbal Injin. J. Ecol. Field Biol., 33, 141–147 (2010).

    Article  Google Scholar 

  • Seo, K. S. and Yun, K. W., Antioxidant activities of extracts from Artemisia capillaris Thunb. and Artemisia iwayomogi Kitam. used as Injin. Kor. J. Plant Res., 21, 292–298 (2008).

    Google Scholar 

  • Stefek, M., Natural flavonoids as potential multifunctional agents in prevention of diabetic cataract. Interdiscip. Toxicol., 4, 69–77 (2011).

    Article  PubMed  CAS  Google Scholar 

  • Tan, R. X., Zheng, W. F., and Tang, H. Q., Biologically active substances from the genus Artemisia. Planta Med., 64, 295–302 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Tang, W. and Eisenbrand, G., Chinese Drugs of Plant Origin, Chemistry, Phamacology and use in traditional and modern medicine. Springer Verlag, New York, p. 179, (1992).

    Google Scholar 

  • Tsukamoto, H., Hisada, S., and Nishibe, S., Coumarin and secoiridoid glucosides from bark of Olea africana and Olea capensis. Chem. Pharm. Bull., 33, 396–399 (1985).

    Article  CAS  Google Scholar 

  • Veitch, N. C., Elliott, P. C., Kite, G. C., and Lewis, G. P., Flavonoid glycosides of the black locust tree, Robinia psedoacacia (Leguminosiae). Phytochemistry, 71, 479–486 (2010).

    Article  PubMed  CAS  Google Scholar 

  • Vinson, J. A. and Howard III, T. B., Inhibition of protein glycation and advanced glycation end products by ascorbic acid and other vitamins and nutrients. J. Nutr. Biochem., 7, 659–663 (1996).

    Article  CAS  Google Scholar 

  • Wawer, I. and Zielinska, A., 13C CP/MAS NMR studies of flavonoids. Magn. Reson. Chem., 10, 33–38 (2001).

    Google Scholar 

  • Wright, C. W., Artemisia, in: Hardman, R. (Ed.), Medicinal and aromatic plants-industrial profiles, Vol. 18, Taylor & Francis, New York, USA (2005).

    Google Scholar 

  • Yamahara, J., Kobayashi, G., Matsuda, H., Katayama, T., and Fujimura, H., The effect of scoparone, a coumarin derivative isolated from the Chinese crude drug Artemisiae capillaris flos, on the heart. Chem. Pharm. Bull., 37, 1297–1299 (1989).

    Article  PubMed  CAS  Google Scholar 

  • Yokozawa, T., Kim, H. Y., Cho, E. J., Choi, J. S., and Chung, H. Y., Antioxidant effects of isorhamnetin 3,7-di-O-β-D-glucopyranoside isolated from mustard leaf (Brassica juncea) in rats with streptozotocin-induced diabetes. J. Agric. Food Chem., 50, 5490–5495 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Yook, C. S., Coloured medicinal plants in Korea, Academic Publishing Co. Seoul, Korea, pp. 431–432, (1989)

    Google Scholar 

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Jung, H.A., Park, J.J., Islam, M.N. et al. Inhibitory activity of coumarins from Artemisia capillaris against advanced glycation endproduct formation. Arch. Pharm. Res. 35, 1021–1035 (2012). https://doi.org/10.1007/s12272-012-0610-0

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